Optimum duration of therapy is not known, but maintenance therapy with antipsychotics is well established.14 In responsive patients, continue as long as clinically necessary and tolerated, but at lowest possible effective dosage; periodically reassess need for continued therapy.12

In patients with remitted first or multiple episodes, the APA recommends either indefinite maintenance therapy or gradual discontinuance of the antipsychotic with close follow-up and a plan to reinstitute treatment upon symptom recurrence.2 Consider antipsychotic therapy discontinuance only after ≥1 year of symptom remission or optimal response while taking antipsychotic.2 Indefinite maintenance treatment is recommended if multiple previous psychotic episodes or 2 episodes within 5 years.2

Prescribing Limits

Adults

Schizophrenia

Oral

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with mild to moderate hepatic impairment (Child-Pugh class A and B); not studied in patients with severe hepatic impairment.13941 (See Distribution: Special Populations under Pharmacokinetics.)

Contraindications

Warnings/Precautions

Warnings

Possible increased risk of death with use of atypical antipsychotics in geriatric patients with dementia-related psychosis.1

Atypical antipsychotics, including paliperidone, are not approved for the treatment of dementia-related psychosis.1 (See Increased Mortality in Geriatric Patients in Boxed Warning and see Geriatric Use under Cautions.)

Prolongation of QT Interval

Avoid use in patients with congenital prolonged QT interval, bradycardia, uncorrected electrolyte disorders (e.g., hypokalemia, hypomagnesemia), or a history of cardiac arrhythmias.1 Also avoid use in those receiving other drugs known to prolong the QTc interval.1 (See Drugs that Prolong QT Interval and also Specific Drugs under Interactions.)

Hyperglycemia and Diabetes Mellitus

Closely monitor patients with preexisting diabetes mellitus for worsening of glucose control and perform fasting glucose tests at baseline and periodically for patients with risk factors for diabetes (e.g., obesity, family history of diabetes).124252627282930313233343536 If manifestations of hyperglycemia occur, perform fasting blood glucose testing.124252627282930313233343536

GI Effects

Extended-release paliperidone tablets are a nondeformable material that does not appreciably change shape in the GI tract.1 Rare cases reported of obstructive symptoms in patients with known strictures in association with nondeformable, controlled-release formulations.1 Avoid administration to patients with severe, preexisting GI narrowing (either pathologic or iatrogenic).1

Esophageal dysmotility and aspiration possible; use caution in patients at risk for aspiration pneumonia (e.g., those with advanced Alzheimer’s dementia).1

General Precautions

Orthostatic Hypotension

Orthostatic hypotension and syncope reported.124 Use with caution in geriatric patients and in patients with known cardiovascular (e.g., heart failure, history of MI or ischemia, conduction abnormalities) or cerebrovascular disease or other conditions (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy) that would predispose them to hypotension.1 Consider monitoring orthostatic vital signs in patients vulnerable to hypotension.12 (See Geriatric Use under Cautions.)

Nervous System Effects

Seizures may occur; use with caution in patients with a history of seizures or other conditions that may lower the seizure threshold (e.g., dementia of the Alzheimer’s type, geriatric patients).136 (See Geriatric Use under Cautions.)

Disruption of ability to regulate core body temperature possible.1 Use caution in patients exposed to conditions that may contribute to an elevation in core body temperature (e.g., dehydration, extreme heat, strenuous exercise, concomitant use of anticholinergic agents.)1

Hyperprolactinemia

Concomitant Illnesses

Possible increased risk of NMS and increased sensitivity to antipsychotic agents in patients with parkinsonian syndrome or dementia with Lewy bodies; manifestations of sensitivity may include confusion, obtundation, postural instability with more frequent falling, or extrapyramidal adverse effects.1 (See Geriatric Use under Cautions.)

Lactation

Pediatric Use

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults; however, manufacturer states greater sensitivity of some older individuals cannot be ruled out.1 Use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in elderly patients.1 (See Concomitant Illnesses and also Nervous System Effects under Cautions and see Renal Impairment under Dosage and Administration.)

Antagonism at other receptors (e.g., α1- and α2-adrenergic receptors, histamine H1 receptors) may contribute to other therapeutic and adverse effects.1239

Paliperidone possesses no affinity for cholinergic, muscarinic, or β1- and β2-adrenergic receptors.139

Advice to Patients

Risk of orthostatic hypotension.112 Importance of using nonpharmacologic methods (e.g., sitting on edge of bed for several minutes upon waking, slowly rising from sitting to standing position) to minimize effects.12

Risk of somnolence.1 Importance of avoiding driving, operating machinery, or performing hazardous tasks until the patient gains experience with the drug’s effects.112

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.124548 Importance of clinicians informing patients about the benefits and risks of taking antipsychotics during pregnancy (see Pregnancy under Cautions).4548 Importance of advising patients not to stop taking paliperidone if they become pregnant without consulting their clinician; abruptly stopping antipsychotic agents may cause complications.48

Importance of swallowing paliperidone tablets whole with the aid of liquids; do not chew, divide, or crush tablets.112 Patients should not be concerned if they notice a tablet-like substance in their stool.112

Importance of informing patients of other important precautionary information.112 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

9. Berwaerts J, Cleton A, Van de Vliet I et al. A randomized, open-label, single-center, crossover study of the potential effects of paroxetine on the pharmacokinetics of a single dose of paliperidone extended-release tablets in healthy subjects. Poster presented at the American Psychiatric Association 160th Annual Meeting. San Diego, CA: 2007 May 19-24.

13. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004; 27:596-601. http://www.ncbi.nlm.nih.gov/pubmed/14747245?dopt=AbstractPlus